Alcohol consumption and risk of renal cell cancer: the NIH-AARP diet and health study

Background:

The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear.

Method:

The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases).

Results:

Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and ⩾30 g per day was, 0.75 (0.63–0.90) and 0.71 (0.59–0.85), respectively, in men and 0.67 (0.42–1.07) and 0.43 (0.22–0.84), respectively, in women.

Conclusion:

Alcohol consumption was inversely associated with RCC in a dose–response manner. The inverse association may be extended to ⩾30 g per day of alcohol intake.     

Meat-cooking mutagens and risk of renal cell carcinoma

Background:

High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys'' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case–control study conducted in metropolitan Detroit and Chicago.

Methods:

Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database.

Results:

The risk of RCC increased with intake of barbecued meat (P_trend=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), P_trend=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (P_interaction<0.05). We found no association for HCAs or overall meat intake.

Conclusion:

BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC.     

Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study

Background:

Studies document that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. However, studies on the direct association of magnesium with pancreatic cancer are few and findings are inconclusive. In this study, we aimed to investigate the longitudinal association between magnesium intake and pancreatic cancer incidence in a large prospective cohort study.

Method:

A cohort of 66 806 men and women aged 50–76 years at baseline who participated in the VITamins And Lifestyle (VITAL) study was followed from 2000 to 2008. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of pancreatic cancer incidence by magnesium intake categories.

Result:

During an average of 6.8-year follow-up, 151 participants developed pancreatic cancer. Compared with those who met the recommended dietary allowance (RDA) for magnesium intake, the multivariable-adjusted HRs (95% CIs) for pancreatic cancer were 1.42 (0.91, 2.21) for those with magnesium intake in the range of 75–99% RDA and 1.76 (1.04, 2.96) for those with magnesium intake <75% RDA. Every 100 mg per day decrement in magnesium intake was associated with a 24% increase in the incidence of pancreatic cancer (HR: 1.24; 95% CI: 1.02, 1.50; P_trend=0.03). The observed inverse associations appeared not to be appreciably modified by age, gender, body mass index, and non-steroidal anti-inflammatory drug use but appeared to be limited to those taking magnesium supplementation (from multivitamins or individual supplement).

Conclusions:

Findings from this prospective cohort study indicate that magnesium intake may be beneficial in terms of primary prevention of pancreatic cancer.     

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Background:

Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.

Methods:

Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.

Results:

No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HR_Q5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).

Conclusions:

Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.     

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

Background:

No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.

Methods:

A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.

Results:

In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day⁻¹, 95% CI: 0.98–1.18, P_trend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, P_trend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, P_trend=0.99).

Conclusions:

There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.     

Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort

Background:

Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort.

Methods:

During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We found no association between total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96–1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes.

Conclusion:

Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.     

Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study

Background:

We examined the associations of intakes of vegetables and carotenes with risk of prostate cancer in Japanese.

Methods:

A total of 15 471 Japanese men participating in the Japan Collaborative Cohort study completed a questionnaire including food intake. Of them, 143 incident prostate cancers were documented. We examined the associations stated above by using Cox proportional hazard model.

Results:

Vegetable intake was not associated with the risk of prostate cancer, but so was dietary alpha-carotene intake. The multivariable hazard ratio (95%CI) in the secondary highest and highest quintiles of alpha-carotene intake was 0.50 (0.26–0.98) (P=0.043) and 0.46 (0.22–0.97) (P=0.041) (P for trend=0.224), respectively. Beta-carotene intake was not associated with the risk of prostate cancer.

Conclusion:

Alpha-carotene intake was associated with lower risk of prostate cancer among Japanese.     

Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type

Background:

Although salt intake is considered a probable risk factor for gastric cancer, relevant studies have provided heterogeneous results, and the magnitude of the association has not been accurately quantified.

Methods:

To quantify gastric cancer risk in relation to dietary salt exposure according to Helicobacter pylori infection status and virulence, smoking, tumour site, and histological type, we evaluated 422 gastric cancer cases and 649 community controls. Salt exposure was estimated in the year before the onset of symptoms through: sodium intake (estimated by a food frequency questionnaire (FFQ)); main food items/groups contributing to dietary sodium intake; visual analogical scale for salt intake preference; use of table salt; and duration of refrigerator ownership.

Results:

Comparing subjects with the highest with those with the lowest salt exposure (3rd vs 1st third), sodium intake (OR=2.01, 95% CI: 1.16–3.46), consumption of food items with high contribution to sodium intake (OR=2.54, 95% CI: 1.56–4.14) and salt intake evaluated by visual analogical scale (OR=1.83, 95% CI: 1.28–2.63) were associated with an increased gastric cancer risk. Subjects owning a refrigerator for >50 years had a lower risk for gastric cancer (OR=0.28, 95% CI: 0.14–0.57). These associations were observed regardless of H. pylori infection status and virulence, smoking, tumour site or histological type.

Conclusion:

Our results support the view that salt intake is an important dietary risk factor for gastric cancer, and confirms the evidence of no differences in risk according to H. pylori infection and virulence, smoking, tumour site and histological type.     

Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study

Background:

Fat intake has been postulated to increase risk of ovarian cancer, but previous studies have reported inconsistent results.

Methods:

The NIH-AARP Diet and Health Study, a large prospective cohort, assessed diet using a food frequency questionnaire at baseline in 1995–1996. During an average of 9 years of follow-up, 695 ovarian cancer cases were ascertained through the state cancer registry database. The relative risks (RRs) and 95% confidence interval (CI) were estimated using a Cox proportional hazard model.

Results:

Women in the highest vs the lowest quintile of total fat intake had a 28% increased risk of ovarian cancer (RR_{Q5 vs Q1}=1.28, 95% CI: 1.01–1.63). Fat intake from animal sources (RR_{Q5 vs Q1}=1.30; 95% CI: 1.02–1.66), but not from plant sources, was positively associated with ovarian cancer risk. Saturated and monounsaturated fat intakes were not related to risk of ovarian cancer, but polyunsaturated fat intake showed a weak positive association. The association between total fat intake and ovarian cancer was stronger in women who were nulliparous or never used oral contraceptives.

Conclusion:

Fat intake, especially from animal sources, was related to an increased risk of ovarian cancer. The association may be modified by parity and oral contraceptive use, which warrants further investigation.     

Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study

Background:

Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear.

Methods:

We analysed the association between alcohol and thyroid cancer in a large (n=490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes.

Results:

Over 7.5 years of follow-up (median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (⩾2 drinks per day vs none, relative risk=0.57, 95% CI 0.36–0.89, P-trend=0.01).

Conclusions:

These results suggest a potential protective role for alcohol consumption in thyroid cancer.     

Choline and betaine intake and risk of breast cancer among post-menopausal women

Background:

Choline and betaine, similar to folate, are nutrients involved in one-carbon metabolism and hypothesised to reduce breast cancer risk. No prospective study among post-menopausal women has examined choline and betaine intakes in relation to breast cancer risk.

Methods:

We examined the intake of choline and betaine and breast cancer risk among 74 584 post-menopausal women in the Nurses'' Health Study. Nutrient intake was assessed using a validated food-frequency questionnaire six times since 1984. During 20 years of follow-up from 1984 until 2004, we documented 3990 incident cases of invasive breast cancer.

Results:

Overall, choline (mean±s.d.; 326±61 mg per day) and betaine (104±33 mg per day) intake was not associated with a reduced risk of post-menopausal breast cancer. Participants in the highest quintile of intakes had multivariate relative risks of 1.10 (95% confidence interval (95% CI): 0.99–1.22; P-value, test for trend=0.14) for choline and 0.98 (95% CI: 0.89–1.09; P-value, test for trend=0.96) for betaine, compared with those in the lowest quintiles of intakes. The results were similar in breast cancer stratified by hormone receptor (oestrogen receptor/progesterone receptor) status. The association between choline intake and breast cancer risk did not differ appreciably by alcohol intake (non-drinker, <15 or 15+ g per day) or several other breast cancer risk factors, including family history of breast cancer, history of benign breast disease, body mass index, post-menopausal hormone use, and folate intake.

Conclusion:

We found no evidence that higher intakes of choline and betaine reduce risk of breast cancer among post-menopausal women.     

Nut consumption and risk of pancreatic cancer in women

Background:

Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer.

Methods:

We prospectively followed 75 680 women in the Nurses'' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.

Results:

We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables.

Conclusion:

Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.     

Adiposity, adult weight change and breast cancer risk in postmenopausal Japanese women: the Miyagi Cohort Study

Background:

The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women.

Methods:

A total of 10 106 postmenopausal women aged 40–64 years (the Miyagi Cohort) were followed from 1990 to 2003, and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years.

Results:

Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05).

Conclusion:

Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk.     

Fluid intake,genetic variants of UDP-glucuronosyltransferases,and bladder cancer risk

Background:

Results of studies of fluid consumption and its association with bladder cancer have been inconsistent. Few studies have considered modification effects from genetic variants that may interact with the type of consumed fluids. UDP-glucuronosyltransferases (UGTs), which are membrane-bound conjugating enzymes, catalyse the transformation of hydrophobic substrates to more water-soluble glucuronides to facilitate renal or biliary excretion. Whether genetic variants in UGTs could modulate the association between fluid intake and bladder cancer has not been studied.

Methods:

We conducted a case–control study with 1007 patients with histopathologically confirmed bladder cancer and 1299 healthy matched controls. Fluid intake and epidemiologic data were collected via in-person interview. Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI).

Results:

After adjustment for potential confounders, high quantity of total fluid intake (⩾2789 vs <1696 ml per day) conferred a 41% increased risk of bladder cancer (OR=1.41; 95% CI=1.10–1.81). Specific fluids such as regular soft drinks and decaffeinated coffee were also associated with increased risks, whereas tea, wine, and liquor were associated with decreased risks. Among 83 single-nucleotide polymorphisms in the UGT gene family, 18 were significantly associated with bladder cancer risk. The most significant one was rs7571337, with the variant genotype conferring a 29% reduction in risk (OR=0.71; 95% CI=0.56–0.90).

Conclusions:

Total and specific fluid intakes are associated with bladder cancer risk in the study population and that genetic variants of UGT genes could modulate the effects. These results facilitate identification of high-risk individuals and have important implications in bladder cancer prevention.     

Family history of cancer and renal cell cancer risk in Caucasians and African Americans

Background:

The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs).

Methods:

In a population-based case–control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls.

Results:

Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer (odds ratio=2.29; 95% confidence interval=1.31–4.00). No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel–Lindau syndrome, revealed no association with RCC risk.

Conclusion:

The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs.     

Risk of renal cell carcinoma in relation to blood telomere length in a population-based case-control study

Background:

There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case–control studies suggested an association between short blood telomere length (TL) and increased RCC risk.

Methods:

We conducted a large population-based case–control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models.

Results:

Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001).

Conclusion:

These data do not support the hypothesis that blood TL is associated with RCC. This population-based case–control study is, to our knowledge, the largest investigation to date of TL and RCC.     

Fish consumption and the risk of colorectal cancer: the Ohsaki Cohort Study

Background:

Evidence from laboratory and animal studies suggests that high fish consumption may reduce the risk of colorectal cancer, but the results of studies in humans have been inconsistent. The objective of this study was to prospectively examine the association between fish consumption and the risk of colorectal cancer incidence in Japan, where fish is widely consumed.

Methods:

We analysed data from 39 498 men and women registered in the Ohsaki National Health Insurance Cohort Study who were 40–79 years old and free of cancer at the baseline. Fish consumption was assessed at the baseline using a self-administered food frequency questionnaire.

Results:

During 9 years of follow-up, we identified 566 incident cases of colorectal cancer (379 men and 187 women). The hazard ratios and 95% confidence intervals (CIs) for colorectal cancer incidence in the highest quartile of fish consumption compared with the lowest quartile were 1.07 (95% CIs; 0.78–1.46, P-trend=0.43) for men, and 0.96 (95% CIs; 0.61–1.53, P-trend=0.69) for women.

Conclusion:

The results of this prospective cohort study revealed no association between fish consumption and the risk of colorectal cancer.     

Hyponatremia as a prognostic and predictive factor in metastatic renal cell carcinoma

Background:

Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC).

Methods:

Cohort A comprised 120 consecutive patients with mRCC receiving subcutaneous, low-dose interleukin-2 and interferon-α. Hyponatremia was assessed in univariate and multivariate analyses. An independent cohort of another 120 patients with mRCC was used for validation (cohort B).

Results:

In cohort A, estimated 5-year survival was 15% and median survival was 15.1 months. Serum sodium ranged between 126 and 144 mM. Twenty-four patients (20%) had serum sodium levels below normal range (<136 mM). In multivariate analysis, significant independent risk factors for short survival were low serum sodium (P=0.014), high neutrophils (P=0.018), lactate dehydrogenase >1.5 upper normal level (P=0.002), and number of metastatic sites (+3) (P=0.003). In cohort B, serum sodium ranged between 128 and 146 mM. Seventeen patients (14%) had sodium levels below normal range. In multivariate analysis, serum sodium was validated as an independent prognostic factor (P=0.001). A significant association between lack of response and hyponatremia was observed in both cohorts (P=0.003 and P=0.02, respectively).

Conclusion:

Low serum sodium is a new, validated, independent prognostic, and predictive factor in patients with mRCC.     

Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study

Background:

Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).

Method:

We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.

Results:

After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46–3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27–2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco–HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.

Conclusion:

Our findings strongly implicate tobacco smoke as a causal factor of HCC development.     

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers

Background:

Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations.

Methods:

We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27 037 Finnish male smokers, aged 50–69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models.

Results:

Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73–0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48–0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee.

Conclusion:

These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.